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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 451 records · Page 25Linked to original sources

Granulocyte colony-stimulating factor and interleukin-6-producing lung cancer cell line, LCAM.

BACKGROUND AND OBJECTIVES: We describe a case of granulocyte colony-stimulating factor (GCSF) and interleukin-6 (IL-6)-producing lung cancer. METHODS: A 53-year-old man underwent left upper lobectomy under diagnosis of lung cancer. The tumor obtained by a preoperative biopsy was analyzed. RESULTS: Preoperative data showed leukocytosis with left-shift of leukocytic morphology and thrombocytosis and an elevated serum GCSF level. Histological examination revealed poorly differentiated adenocarcinoma. A cell line, named LCAM, was established from the tumor and the cytokines in the culture medium were measured by enzyme immunoassay. GCSF and IL-6 were produced in large amounts by LCAM, but granulocyte-macrophage colony-stimulating factor (GMCSF) and interleukin-3 (IL-3) were not. A proportion of LCAM expressed GCSF receptor on the cell surface, but IL-6 receptor could not be detected. LCAM proliferation was inhibited in the culture with antihuman GCSF antibody in a dose-dependent manner. CONCLUSIONS: We suggest that LCAM proliferation is positively regulated by GCSF.

Granulocyte Colony-Stimulating Factor↗

Failure to down-regulate Bcl-2 protein in thymic germinal center B cells in myasthenia gravis.

The most unusual characteristic of myasthenia gravis (MG) is that the thymus has germinal centers (GC). Cultured thymic lymphocytes from MG patients spontaneously produce anti-acetylcholine receptor antibodies, indicating that autoreactive B cells have escaped negative selection. To investigate the underlying mechanism, we examined the expression of the apoptosis-related protein Bcl-2 in GC B cells (defined as CD19+ CD38+ cells) in the thymus in 14 MG patients using three-color flow cytometry. GC in MG patients did not show the normal down-regulation of Bcl-2 (the frequency of Bcl-2+ GC B cells in the MG thymus and in control tonsils 54.3 +/- 16.2% versus 20.6 +/- 8.0%; mean +/- SD. p < 0.0001). In contrast, Bcl-2 in GC in the mediastinal lymph nodes from four patients was down-regulated to a relatively normal level. Using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method to detect DNA fragmentation in situ, the frequency of TUNEL+ cells in GC in the MG thymus was lower than in control tonsils. These results suggest that autoreactive B cells which normally undergo apoptosis in GC may survive because of Bcl-2 up-regulation in this unusual location.

Adolescent↗

Use of a fusion protein to obtain crystals suitable for X-ray analysis: crystallization of a GST-fused protein containing the DNA-binding domain of DNA replication-related element-binding factor, DREF.

Crystals of glutathione-S-transferase (GST)-fused protein containing the DNA-binding domain of DNA replication-related element-binding factor, DREF, were obtained under crystallization conditions similar to those for GST. Preliminary X-ray crystallographic analysis revealed that crystals of the GST-fused protein belong to space group P6(1)22 or P6(5)22 with unit cell dimensions a = b = 140.4 A, c = 93.5 A and gamma = 120 degrees, having one molecule in the crystallographic asymmetric unit. The crystals diffract to 2.5 A resolution. The cell dimensions are related to those of GST crystals thus far reported. Crystallization of the DNA-binding domain that was cleaved from the fused protein by thrombin was also carried out using several methods under numerous conditions, but efforts to produce well-ordered large crystals were unsuccessful. A possible application of GST-fusion proteins for small target proteins or domains to obtain crystals suitable for X-ray structure determination is proposed.

Crystallography, X-Ray↗

Granisetron reduces postoperative nausea and vomiting throughout menstrual cycle.

PURPOSE: The incidence of postoperative nausea and vomiting (PONV) is influenced by menstruation. This study was undertaken to assess the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for preventing PONV in patients during two different phases of menstrual cycle. METHODS: One hundred twenty female patients undergoing general anaesthesia for major gynaecological surgery were divided according to the phase of menstrual cycle into two groups: day one to eight (menstrual) and day nine to end of the cycle (non-menstrual) groups. In a randomized, double-blind manner, the patients received placebo (saline) or 40 micrograms.kg-1 granisetron i.v. immediately before the induction of anaesthesia. All patients received a standardized general and epidural anaesthesia and epidural morphine plus bupivacaine for postoperative analgesia. The incidence of PONV and other adverse events was recorded during the first 24 hr after anaesthesia. RESULTS: The treatment groups were similar with respect to patient demographics, types of surgery, anaesthetics administered and analgesics used postoperatively. The incidence of PONV was 72% and 32% in patients during menstruation receiving placebo or granisetron (P < 0.05), and was 46% and 20% in those during non-menstruation, respectively (P < 0.05). No differences in the incidence of other adverse events were observed among the groups. CONCLUSION: Granisetron was effective in reducing the incidence of PONV in both phases of the menstrual cycle studied.

Adult↗

Prevention of PONV with granisetron, droperidol and metoclopramide in female patients with history of motion sickness.

PURPOSE: Motion sickness is one of the patient-related factors associated with postoperative nausea and vomiting (PONV). This study was undertaken to assess the efficacy of granisetron, droperidol and metoclopramide for preventing PONV in female patients with a history of motion sickness undergoing major gynaecological surgery. METHODS: In a prospective, randomized, placebo-controlled, double-blind study, 120 patients received either 1.25 mg droperidol, 10 mg metoclopramide, 40 micrograms.kg-1 granisetron or placebo (saline) iv immediately before induction of anaesthesia. A standardized anaesthetic technique and postoperative analgesia were used in all patients. During the first 24 hr after anaesthesia, the incidence of PONV and adverse events were recorded by nursing-staff. RESULTS: The treatment groups were similar for patient demographics, types of surgery, anaesthetics administered and opioid given. The incidence of PONV was 70%, 50%, 57% and 23% in the placebo, droperidol, metoclopramide and granisetron groups, respectively (P < 0.05; overall chi 2 test). No difference in the incidence of adverse events was observed in either group. CONCLUSION: Granisetron is a better prophylactic antiemetic than droperidol or metoclopramide in female patients with a history of motion sickness undergoing major gynaecological surgery.

Adult↗

Granisetron reduces the incidence and severity of nausea and vomiting after laparoscopic cholecystectomy.

PURPOSE: Postoperative nausea and vomiting (PONV) are commonly observed undesirable consequences of laparoscopic cholecystectomy. This study was undertaken to compare granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, with droperidol for reducing the incidence and severity of PONV after laparoscopic cholecystectomy. METHODS: Eighty patients, aged 25-65 yr, scheduled for elective laparoscopic cholecystectomy were enrolled in a randomized, double-blinded investigation and assigned to one of three treatment regimens: placebo (saline), 1.25 mg droperidol (approximately 25 micrograms.kg-1) or 3 mg granisetron (approximately 60 micrograms.kg-1). The study drugs were administered iv immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. Nausea, vomiting and safety assessments were performed continuously during the first 24 hr after anaesthesia. RESULTS: The incidence of PONV was 46% with placebo, 41% with droperidol and 15% with granisetron (P < 0.05; overall chi 2 test). Four patients who had received placebo and two who had received droperidol required another rescue antiemetic, compared with none who had received granisetron (P < 0.05). Adverse events postoperatively were not different among the groups. CONCLUSION: Granisetron is more effective than droperidol and placebo for reducing the incidence and severity of PONV after laparoscopic cholecystectomy.

Adult↗

Prophylactic antiemetic efficacy of granisetron in patients with and without previous postoperative emesis.

PURPOSE: To evaluate the efficacy of granisetron, a selective antagonist of 5-hydroxytryptamine type 3 receptors, in the prevention of PONV in patients with and without previous postoperative emesis undergoing general anaesthesia for major gynaecological surgery. METHODS: In a randomized, double-blind, placebo-controlled trial of 90 women with (n = 40) and without (n = 50) a history of PONV, the patients received either granisetron (40 micrograms.kg-1) or placebo (saline) iv immediately before induction of anaesthesia. The same standard general anaesthetic technique, which consisted of isoflurane in nitrous oxide and oxygen and avoided opioids, was used. Nausea, vomiting and safety assessments were performed during the first 24 hr after anaesthesia. RESULTS: The incidence of PONV was 70% and 25% after administration of placebo and granisetron in patients with previous PONV (P < 0.05), and was 40% and 8% in patients without it, respectively (P < 0.05). The incidence of adverse events postoperatively were not different among the treatment groups. CONCLUSION: Granisetron 40 micrograms.kg-1 given prior to anaesthesia reduces the incidence of PONV in patients with a history of PONV as well as in patients without it.

Adult↗

Cardiovascular responses to tracheal extubation or LMA removal in normotensive and hypertensive patients.

PURPOSE: This study was undertaken to evaluate the haemodynamic changes of tracheal extubation or removal of a laryngeal mask airway (LMA) in normotensive and hypertensive patients. METHODS: In a randomized trial of normotensive and hypertensive patients (n = 40 of each), tracheal extubation or LMA removal was performed. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and 1, 2, 3, 5, and 10 min after tracheal extubation or LMA removal. RESULTS: In normotensive patients, HR, MAP and RPP increased following tracheal extubation or LMA removal, and remained elevated for a maximum three minutes (P < 0.05). In hypertensive patients, the haemodynamic increases in response to extubation or LMA removal were observed for up to five minutes (P < 0.05). The immediate cardiovascular responses to extubation were greater than those related to LMA removal in both normotensive and hypertensive patients (normotensive: HR; 95 +/- 14 vs 81 +/- 11, MAP; 124 +/- 18 vs 106 +/- 10, RPP; 14,951 +/- 2720 vs 10,654 +/- 1898, hypertensive: HR 105 +/- 10 vs 87 +/- 13, MAP; 146 +/- 17 vs 119 +/- 12, RPP; 20,492 +/- 1674 vs 12,862 +/- 2115, mean +/- SD, P < 0.05). Following extubation or LMA removal, these haemodynamic variables increased more markedly in hypertensive patients than in normotensive patients (P < 0.05). CONCLUSION: Removal of LMA is associated with less cardiovascular change than tracheal extubation in both normotensive and hypertensive patients.

Adult↗

Overnight suppression of parathyroid hormone and bone resorption markers by active absorbable algae calcium. A double-blind crossover study.

In order to study the effect of Ca supplementation on the nocturnal rise of PTH and bone resorption, a double-blind, placebo-controlled study was carried out on 9 healthy male volunteers. Regimen A consisted of an oral dose of 150 mg Ca as AAACa after each meal and 450 mg at bedtime; B consisted of 300 mg after each meal and C was placebo. Plasma ionized Ca was significantly higher in A than in B at 6 a.m. the next morning and urinary Ca/Cr after 5 days was higher in A than in B and C. Plasma intact PTH fell by 19 +/- 4 pg/ml in A, 8 +/- 7 in B, and 1 +/- 7 after 1 day, and significantly decreased by 29 +/- 8 in A, increased by 11 +/- 11 in B, and 5 +/- 7 in C after 5 days (A and B, and A and C, p = 0.0242 and 0.0433, respectively), with increases of % tubular reabsorption of phosphorus. Urinary excretion of cross-linked collagen degradation product (Crosslaps) was 40 +/- 10% of the baseline in A, 97 +/- 22 in B, and 173 +/- 30 in C (A and C, P = 0.0061) after 5 days. Systolic blood pressure at 6 a.m. fell by 17 +/- 4 mmHg A, 24 +/- 3 in B, and 4 +/- 2 in C. Highly biologically available AAACa effectively suppressed nocturnal rise of PTH and bone resorption markers in 5 days.

Analysis of Variance↗

Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome-mediated endothelin-1 gene transfer.

BACKGROUND: Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 (ET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. METHODS: We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)-liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with beta-galactosidase gene was introduced. The expression of ET-1 and beta-galactosidase was assessed by immunohistochemistry. RESULTS: Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of beta-galactosidase gene, indicating beta-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. CONCLUSIONS: These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.

Animals↗

Experimental reconstruction of the mediastinal trachea with a wing-shaped reversed esophageal flap.

BACKGROUND: In cases of extensive tracheal resection in which direct end-to-end anastomosis is impossible there is a need for reconstruction. Nevertheless, with the present lack of reliable artificial trachea, no reconstruction method is available to assure safe replacement of the mediastinal trachea. METHODS: After tubular resection of the mediastinal trachea in mongrel dogs, the trachea was reconstructed using a wing-shaped reversed esophageal flap. A silicone tube was used as an internal stent. RESULTS: In group I (16 animals), three tracheal rings were resected; in group II (4 animals), six tracheal rings; in group III (6 animals), eight tracheal rings; and in group IV (5 animals), eight tracheal rings and the lining of the greater omentum. Safe reconstruction was accomplished in all cases in groups I and II, 2 of 6 cases in group III, and 2 of 5 cases in group IV. The omentopexy failed to prevent incomplete closure, yet served to minimize inflammation in the mediastinum. CONCLUSIONS: A reversed esophageal autograft can be considered as a tracheal replacement.

Animals↗

Increased nitric oxide levels in exhaled air of rat lung allografts.

In organ transplantation nitric oxide has been reported to be involved in allograft rejection. We examined in a rat lung transplantation model whether nitric oxide is overproduced in acute rejection and can be detected in exhaled air. Thirteen rat right lung transplants were separated into three groups: group 1 (n = 5), untreated allografts (Brown-Norway [RT1n] to Lewis [RT1l]); group 2 (n = 4), cyclosporine-treated allografts; and group 3 (n = 4), isografts (Lewis to Lewis). We examined exhaled nitric oxide levels with a chemiluminescence analyzer and chest roentgenograms on days 2 through 5. Histologic samples were obtained on days 3 and 5. On day 5, the recipients were killed and we measured exhaled nitric oxide from the right and left lungs separately. Blood samples were also obtained for measurement of serum nitrite/nitrate. The exhaled nitric oxide level in untreated allografts increased significantly from day 5 (63.9 +/- 39.2 ppb, p = 0.0095) and was significantly higher than that in treated allografts (9.1 +/- 1.6 ppb) (p = 0.0085) and isografts (6.9 +/- 0.5 ppb) (p = 0.0068). The nitric oxide level in untreated allografts (826.5 +/- 416.1 ppb) was 75 times as high as that from the contralateral normal left lungs (11.2 +/- 2.6 ppb) (p = 0.0118). The level of exhaled nitric oxide correlated significantly with the histologic rejection grade (p = 0.0001). There was no significant difference in the serum nitrite/nitrate levels between allografts and isografts. These data suggest that increased exhaled nitric oxide levels might reflect acute rejection in lung transplants.

Animals↗

Epithelioid angiosarcoma of bone.

Angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. This article describes an epithelioid angiosarcoma in the humerus of a 48-year-old man. A multilocular osteolytic lesion with undefined margins and destroyed cortical and medullary bone, associated with a large soft tissue mass was demonstrated radiologically in the proximal metaphysis of the right humerus. The tumor, resected by amputation, was composed mostly of proliferating malignant cells with an epithelioid morphology. It had a predominantly sheet-like growth pattern, and an occasional pseudoglandular or alveolar arrangement, mimicking an adenocarcinoma. The dilated anastomotic vascular spaces lined by epithelioid endothelial cells and the intracytoplasmic lumina/vacuoles that sometimes contained erythrocytes suggested focal endothelial differentiation. On immunohistochemical investigation, many neoplastic cells expressed cytokeratin and endothelial markers: factor-VIII related antigen, CD31, and UEA-I. The ultrastructure of the tumor was consistent with that of an angiosarcoma. Our patient died of disease shortly after the diagnosis, implying an aggressive clinical course. Awareness of the existence of skeletal epithelioid angiosarcoma, combined with the identification of intracytoplasmic lumina, or at least small vasoformative foci, and immunohistochemical positivity for endothelial markers provide the best guide for distinguishing this tumor from metastatic carcinomas.

Biomarkers, Tumor↗

Antidromic burst activity of locus coeruleus neurons during cortical spreading depression.

The electrical activity of locus coeruleus neurons was investigated during cortical spreading depression in urethane-anaesthetized rats. Cortical spreading depression was induced by a direct application of 1-3 M KCl solution to the surface of the cerebral cortex. The occurrence of cortical spreading depression was assessed by recording negative d.c. shifts and in some experiments by monitoring the extracellular potassium concentrations. The mean spontaneous firing rate of locus coeruleus neurons was significantly reduced during cortical spreading depression. Approximately 60% of locus coeruleus neurons recorded during cortical spreading depression revealed anomalous burst activity consisting of multiple initial segment spikes as well as full initial segment-somatodendritic spikes with a marked initial segment-somatodendritic break. Each spike of the cortical spreading depression-related burst activity occurred at intervals ranging from 15.0 ms to 90.1 ms (34.9 +/- 0.5 ms). The burst activity appeared unpredictably at variable intervals in a phasic or tonic manner during cortical spreading depression. The cortical spreading depression-related burst activity of locus coeruleus neurons mimicked antidromic spikes induced by train stimulation of the cerebral cortex at short interspike intervals during iontophoretic application of GABA to locus coeruleus neurons, whereas it was totally different from synaptically-activated burst activity induced by tail pinch. The full spikes and initial segment spikes in the cortical spreading depression-related burst activity failed to collide with cortically elicited antidromic spikes, even when they appeared within the collision interval. The proportion of initial segment spikes in the cortical spreading depression-related burst activity was reduced following an increase in membrane excitability by iontophoretic application of glutamate, and increased during a decreased membrane excitability by GABA application. The antidromic burst activity of locus coeruleus neurons also appeared for a short time during cortical spreading depression prior to the occurrence of seizure waves induced by GABA antagonists, while the burst activity could not be observed during seizure activity. These results indicate that the cortical spreading depression-related burst activity was of antidromic origin and that the marked initial segment-somatodendritic break in spontaneous spikes of locus coeruleus neurons during cortical spreading depression was due to reduced excitability of the somatodendritic membrane. The cortical spreading depression-related burst activity may cause release of a large amount of noradrenaline in vast regions of locus coeruleus terminal fields through the numerous axon collaterals, thereby playing a role in functional changes of brain neurons related to cortical spreading depression.

Animals↗

Saccular aneurysm in the right-sided aortic arch: a successfully corrected case.

We report the surgical treatment of a rare case of true aortic aneurysm in a right-sided aortic arch. A 49-year-old female patient with obstructive respiratory problems demonstrated a true aneurysm with a diameter of 58 mm located at the right-sided aortic arch between the right carotid artery and right subclavian artery. Surgery was successfully performed by replacing the arch including the aneurysm with a prosthetic graft. The positions of true aneurysms in the right-sided aortic arch can be divided into two subtypes: first, the transverse arch between the right carotid artery and right subclavian artery, and second, the base of the subclavian artery, the Kommerell's diverticulum. The region is informative for consideration of the surgical approach toward aneurysms of this entity.

Angiography, Digital Subtraction↗

Pilot study for preoperative administration of l-OHP to patients with advanced scirrhous type gastric cancer.

A new DACH platinum complex, l-OHP, was developed by Kidani as an anticancer agent. A clinical trial took place in Europe which demonstrated its therapeutic efficacy for colorectal cancer. An effective treatment, especially chemotherapy for patients with a advanced scirrhous type gastric cancer, has not yet been established. An in vitro study showed that l-HOP inhibited cell growth in human gastric cancer cell lines. Our pilot study determined the efficacy of preoperative administration of l-OHP, 67 mg/m2 to 100 mg/m2, every 2-3 weeks, for two to three cycles, in five patients with this disease (Stage III and IV) roentogenoscopically and histologically. The platinum concentration in the tissues was also measured. By X-ray examination of the stomach at the time of pre- and post-administration of l-OHP, extension of the lesional gastric wall was observed. Histologically three Grade 2 responses and two Grade 1a responses were obtained according to the criteria presented by Japanese Research Society for Gastric Cancer. The mean platinum concentrations in the lesional tissues were 0.98 ppm and 0.5 ppm in the patients administered l-OHP for three and two cycles respectively. There was no toxicity that prevented surgery. These preliminary results showed the possibility that 1-OHP would be effective for patients with advanced scirrhous type gastric cancer as a neoadjuvant therapy.

Adenocarcinoma, Scirrhous↗

Surgery in patients with HIV infection: indications and outcome.

We reviewed the records of 12 patients with HIV infection (one stage I, three stage II, two stage III, six stage IV) who received 15 surgical procedures under general or lumbar/epidural anesthesia. We discussed surgical indications, their poor wound healing and precautions for preventing the risk of transmission of HIV to health care workers. Six emergency and nine elective operations were performed. Postoperative complications developed after three emergency and three elective operations. Ten patients showed delay of wound healing which was not directly correlated with the CD4+ cell count. No operative deaths occurred. In any stage of HIV infection, not only palliative but also curative operations can be performed as long as HIV infection, opportunistic infections and HIV-related neoplasms can be controlled. Late stage wound healing is poor, but the wound will heal without keloid formation, although it takes two to three times longer than usual. For operating on patients with HIV infection precautions for preventing needle sticks, sharp injuries and blood exposure should be learned and used by health care workers. As a result, surgical staff members will be able to perform operations safely on HIV-infected patients to improve both quality of life and the prognosis of their disease.

Adult↗

Elevated plasma thymosin-alpha1 levels in lung cancer patients.

OBJECTIVE: Prothymosin-alpha, the precursor of thymosin-alpha1, may play a role in cell proliferation, and the plasma level of thymosin-alpha1 may reflect the degree of proliferation of the tumor cells. METHODS: Recently, a new sandwich immunoradiometric assay for thymosin-alpha1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-alpha1 in 131 lung cancer patients. RESULTS: We found that the mean plasma thymosin-alpha1 levels in lung cancer patients were higher than in normal individuals (P < 0.001). However, half of the patients showed normal levels. Thymosin-alpha1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-alpha1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P = 0.03). Survival of patients with normal levels of plasma thymosin-alpha1 was significantly better than that with higher levels (P = 0.04). CONCLUSIONS: The plasma level of thymosin-alpha1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Adenocarcinoma↗